This comprehensive program is designed to analyze some of the effector pathways and regulatory mechanisms of immediate and subacute hypersensitivity and inflammation in the lung. The predominant focus will be on the modulation of pulmonary macrophage migration and function, the mechanisms underlying the immunologically stimulated generation and release of chemical mediators by pulmonary cells, and the regulation by alpha-globulins of enzymatic and cellular reactions in the inflammatory response of the lung. Investigations will probe the control of in vitro migration of alveolar macrophages and their in vivo clearance of particles from the lung by chemokinetic principles and inhibitors of migration, as well as by components of surfactant. IgE-mediated induction of synthesis of unstored chemical mediators will be explored in terms of the dependence on arachidonic acid metabolism, alterations in intracellular concentrations of cyclic nucleotides and interactions among various types of pulmonary cells. The effects of alpha1-antitrypsin in neutrophil-predominant inflammatory reactions of the lung will be studied in terms of the neutral peptide-generating system of human neutrophils. As the expression of this mediator system in the lung is a specific reflection of neutrophil infiltration of pulmolary tissues, the concentrations of the components will be analyzed in in vitro models as well as biological fluids and tissues from human disease states utilizing both functional and immunochemical methods.